Pregnancy permanently rewires a mother’s metabolism, and a new mouse model lets scientists finally trace which placental hormones drive those lasting changes. This matters because pregnancy complications—and the long-term metabolic risks they create for mothers—remain poorly understood at the molecular level. The placenta releases a cocktail of hormones that reshape nearly every organ in the mother’s body, but until now researchers lacked the tools to isolate which hormones do what, and when. The team has engineered mice whose placental hormone production can be switched off during pregnancy, allowing them to compare mothers with and without those hormonal signals. If the project succeeds, it will reveal the specific hormones and molecular pathways that create lasting “memories” in maternal tissues, influencing health and aging long after childbirth. This is fundamental science—it will not produce a drug or policy tomorrow. But understanding how pregnancy programs female metabolism could eventually explain why women and men age differently, why some women develop diabetes or heart disease years after giving birth, and how to improve health monitoring for mothers. The same mechanisms likely operate in livestock, so the work may also inform breeding and animal health strategies.
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Pregnancy is a unique state during which nearly every organ and tissue in the mother’s body adapts to support fetal development. Whilst some changes reverse after delivery, pregnancy often leaves causing permanent changes in the female body, a phenomenon observed across mammals. Proper regulation of these adaptations is essential, as their disruption can lead to pregnancy complications that pose immediate and long-term health risks for both mother and offspring. These risks extend beyond women and their families, affecting animal health, productivity and the economic stability of livestock industry and food production. Despite these far-reaching implications, pregnancy remains under-researched, particularly in the context of healthy aging in females. The placenta, a vital organ for fetal development, secretes signalling factors, including hormones, believed to drive adaptations in the mother’s body during pregnancy. However, until recently, models and tools to pinpoint the role of placental hormones in these processes have been lacking. We also have limited understanding of how these hormones contribute to long-term health maternal health risks after pregnancy. To address these gaps, we developed a genetically modified mouse model in which placental hormone production is specifically disrupted during pregnancy. Preliminary studies show that this disruption alters in maternal metabolism both during and after pregnancy. Consequently, we can now study the mechanisms by which placental hormones influence maternal health during pregnancy and aging, forming the basis of this grant. By combing this advanced mouse model with rigorous metabolic testing, imaging and tissue assessments, this project will examine in detail how placental hormone production affects health of the mother during pregnancy and with aging after pregnancy. Using highly-sensitive profiling techniques, we will measure when placental hormone levels change during pregnancy and link these patterns to alterations in maternal metabolism. Targeted experiments will determine the specific functions of individual placental hormones in driving these changes. Finally, we will using cutting-edge DNA and gene sequencing will reveal the pathways through which placental hormones create lasting “memories” in maternal tissues and organs, influencing metabolic health long after pregnancy. Through an integrated, systematic approach and advanced tools, we will uncover the fundamental links between placental hormones and animal physiology. Our research will identify the timing and molecular mechanisms involved, shedding light on how placental hormones function to shape female health during pregnancy and beyond. These insights will help explain differences in health and lifespan between females and males, and clarify how pregnancy complications arise, providing a foundation for better health policies and advocacy for women’s health monitoring during and after pregnancy. Our findings may also have implications for those in the farming/agricultural sector and the development of strategies to improve the health, productivity and fertility of livestock. Researchers and students involved in this project will gain expertise in animal physiology, tissue analyses, molecular techniques and big data. Data generated will benefit diverse fields, including reproduction, development, pregnancy, women’s health, ageing, genetics, metabolism, and health across generations. We will share findings through institutional seminars, local outreach, and conferences attended by biologists, clinical doctors, and stakeholders across industry, academia and government. Public engagement efforts, including science festivals and school visits, will maximize societal impact and inspire the next generation of scientists. This proposal addresses directly BBSRC Responsive Mode Priorities to understand Animal health, the Rules of life and Healthy aging across the lifespan.
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